@article {635031, title = {AMPK-Activated Protein Kinase Suppresses Ccr2 Expression by Inhibiting the NF-κB Pathway in RAW264.7 Macrophages.}, journal = {PLoS One}, volume = {11}, number = {1}, year = {2016}, month = {2016}, pages = {e0147279}, abstract = {C-C chemokine receptor 2 (Ccr2) is a key pro-inflammatory marker of classic (M1) macrophage activation. Although Ccr2 is known to be expressed both constitutively and inductively, the full regulatory mechanism of its expression remains unclear. AMP-activated protein kinase (AMPK) is not only a master regulator of energy homeostasis but also a central regulator of inflammation. In this study, we sought to assess AMPK{\textquoteright}s role in regulating RAW264.7 macrophage Ccr2 protein levels in resting (M0) or LPS-induced M1 states. In both M0 and M1 RAW264.7 macrophages, knockdown of the AMPKα1 subunit by siRNA led to increased Ccr2 levels whereas pharmacologic (A769662) activation of AMPK, attenuated LPS-induced increases in Ccr2 expression in an AMPK dependent fashion. The increases in Ccr2 levels by AMPK downregulation were partially reversed by NF-κB inhibition whereas TNF-a inhibition had minimal effects. Our results indicate that AMPK is a negative regulator of Ccr2 expression in RAW264.7 macrophages, and that the mechanism of action of AMPK inhibition of Ccr2 is mediated, in part, through the NF-κB pathway.}, issn = {1932-6203}, doi = {10.1371/journal.pone.0147279}, author = {Kumase, Fumiaki and Takeuchi, Kimio and Morizane, Yuki and Suzuki, Jun and Matsumoto, Hidetaka and Kataoka, Keiko and Al-Moujahed, Ahmad and Maidana, Daniel E and Miller, Joan W and Vavvas, Demetrios G} }